SOLUBLE FAS APO-1 IN TUMOR-CELLS - A POTENTIAL REGULATOR OF APOPTOSIS/

Fas/APO-1, a member of the NGF/TNF receptor superfamily expressed on t he cell-surface of normal and malignant cells, is known to induce cell death by apoptosis. In the present study, we have investigated Fas/AP O-1 gene defects in a human osteosarcoma cell line resistant to the ap optosis-inducing effects of anti-Fas. cDNA cloning and sequencing reve aled that these cells contained both 'authentic' and mutant Fas/APO-1 containing a 63 base pair in-frame deletion spanning the transmembrane domain, designated DFas/APO-1. Direct evidence for the existence of a soluble Fas/APO-1 protein was obtained by immunoprecipitation and Wes tern blotting. Taken together with prior studies demonstrating a role for Fas/APO-l and Fas ligand, respectively, in tumor target cell killi ng by cytotoxic T-lymphocytes, production of soluble Fas/APO-1 might h ave significant implications in malignant disease pathogenesis.